Analysis of adverse effects of obesity treatnent drug with significant costs

[B. B. Raičević]

94 str.

Uvod: Iako su lekovi protiv gojaznosti pokazali značajnu kliničku efikasnost i pomogli velikom broju pacijenata da normalizuju telesnu težinu ili bar da je smanje, njihova neželjena dejstva često nisu prepoznata kao značajan izvor morbiditeta i povećanja troškova lečenja. Cilj: Ciljevi ove doktorske teze su utvrditi faktore povezane sa pojavom neželjenih dejstava lekova za lečenje gojaznosti koja stvaraju značajne troškove i utvrditi strukturu i iznos troškova koje stvaraju neželjena dejstva lekova za lečenje gojaznosti. Metod: Ova doktorska teza je izrađena primenom metode triangulacije, tj. korišćenjem tri različite metode istraživanja za objašnjenje istog fenomena – neželjenih dejstava lekova za lečenje gojaznosti. U radu su bile korišćene sledeće tri metode: opservaciona studija preseka, studija troškova i sistematski pregled literature. Opservaciona studija preseka se bavila faktorima povezanim sa gastrointestinalnim neželjenim efektima metformina, leka koji se vanindikaciono koristi za lečenje gojaznosti. Studija troškova je obuhvatila neželjena dejstva lekova protiv gojaznosti koja zahtevaju značajno korišćenje zdravstvenih resursa i izvedena je na osnovu podataka iz 10 evropskih zemalja. Sistematski pregled je obuhvatio metode prilagođavanja ulaznih parametara studija odnosa troškova i efekata lekova zasnovanih na izradi farmakoekonomskih modela. Rezultati: Viši indeks telesne mase, trajni boravak na većim nadmorskim visinama, postojanje anemije i prethodnih crevnih infekcija u poslednja tri meseca, značajno povećavaju rizik od nastanka gastrointestinalnih tegoba kod pacijenata koji su na terapiji metforminom. S druge strane, istovremena primena statina ima zaštitni efekat u pogledu nastaka gastrointestinalnih tegoba. Konkretno, anemija povećava rizik od ovih tegoba 4,2 puta, a prethodna crevna infekcija 2,8 puta. Svaka dodatna jedinica BMI povećava učestalost gastrointestinalnih tegoba za 11%, dok prelazak sa 10 na 2000 metara nadmorske visine udvostručuje verovatnoću pojave ovih problema. Terapija statinima smanjuje učestalost gastrointestinalnih tegoba za oko 80%. Ekonomsko stanje ispitivanih zemalja, izraženo kroz bruto nacionalni dohodak po glavi stanovnika, ima ključnu ulogu u formiranju troškova lečenja većine analiziranih neželjenih efekata, osim retinopatije, anafilakse i respiratornih poremećaja. Povećani troškovi privatnog zdravstvenog sektora u nekoj zemlji uticali su na više troškove lečenja depresije, infekcija gornjih disajnih puteva, melanocitnog nevusa i hepatitisa izazvanog lekovima. Nasuprot tome, veća ulaganja u farmaceutske proizvode, medicinsku opremu i preventivnu negu imala su tendenciju da smanje troškove lečenja različitih neželjenih efekata, nezavisno od njihove lokalizacije ili mehanizma delovanja u organizmu. Neophodna prilagođavanja farmakoekonmskih analiza obuhvataju sniženje diskontnih stopa za troškove i efekte lečenja koje rezultira značajnim produženjem života, diferencijalno diskontovanje troškova i efekata, izračunavanje lokalne granice isplativosti (inkrementalnog odnosa troškova i efekata) i dugoročna projekcija kretanja cene leka...

Introduction: Although anti-obesity drugs have shown significant clinical efficacy and helped a large number of patients to normalize body weight or at least reduce it, their side effects are often unrecognized as a significant source of morbidity and increased treatment costs. Objective: The objectives of this doctoral thesis are to determine the factors associated with the occurrence of adverse effects of drugs for the treatment of obesity that generate significant costs, and to determine the structure and amount of costs that generate adverse effects of drugs for the treatment of obesity. Method: This doctoral thesis was prepared using the triangulation method, i.e. using three different research methods to explain the same phenomenon - the side effects of drugs for the treatment of obesity. The following three methods were used in the thesis: cross-sectional observational study, cost study and systematic literature review. A cross-sectional observational study looked at factors associated with gastrointestinal side effects of metformin, a drug used off-label to treat obesity. The cost study included side effects of anti-obesity drugs that require significant use of healthcare resources, and was based on data from 10 European countries. The systematic review included methods of adjusting the input parameters of drug cost-effectiveness studies based on the development of pharmacoeconomic models. Results: Higher body mass index, permanent residence at higher altitudes, existence of anemia and previous intestinal infections in the last three months significantly increase the risk of gastrointestinal complaints in patients on metformin therapy. On the other hand, the simultaneous use of statins has a protective effect in terms of the onset of gastrointestinal complaints. Specifically, anemia increases the risk of these adverse effects 4.2 times, and previous intestinal infection 2.8 times. Each additional unit of BMI increases the frequency of gastrointestinal problems by 11%, while moving from 10 to 2000 meters above sea level doubles the probability of these problems. Statin therapy reduces the frequency of gastrointestinal complaints by about 80%. The economic condition of the examined countries, expressed through the gross national income per capita, plays a key role in the formation of the costs of treating most of the analyzed side effects, except for retinopathy, anaphylaxis and respiratory disorders. Increased private health sector costs in a country have resulted in higher costs of treating depression, upper respiratory tract infections, melanocytic nevus and drug-induced hepatitis. Conversely, greater investment in pharmaceuticals, medical equipment, and preventive care tended to reduce the cost of treating various side effects, regardless of their location or mechanism of action in the body. Necessary adjustments of pharmacoeconomic analyzes include reduction of discount rates for costs and effects of treatment that results in significant life extension, differential discounting of costs and effects, calculation of the local cost-effectiveness limit (incremental ratio of costs and effects) and long-term projection of drug price movements...

lekovi protiv gojaznosti, neželjena dejstva, faktori rizika, troškovi

anti-obesity drugs, side effects, risk factors, cost

615.214(043.3)

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